Growing interest in the cellular origins of different breast cancer subtypes has prompted investigations into the subpopulations of the normal breast epithelia and their differentiation hierarchy. Several groups have demonstrated a likely luminal-progenitor cell origin for basal-like breast cancer. However, the molecular and cellular mechanisms underlying why one breast cell type might be more susceptible to transformation are yet to be elucidated. To observe the molecular differences in the different cell subpopulation response to ionizing radiation (IR), we performed gene expression profiling of MUC1+-sorted and CD10+-sorted primary human mammary epithelial cell cultures. Transcriptional response was measured at 2 and 24 hr after treatment with 2 and 5 Gy IR using Illumina HumanHT-12 v4 Expression Beadchips. The complete sample cohort included time-point matched untreated (0 Gy) controls in a total of 5 individual patients. Our analyses indicated several cell-type specific differences in response to IR. Overall design: RNA was extracted from MUC1+-sorted and CD10+-sorted primary human mammary epithelial cell cultures at 2 and 24 hr after treatment with 0, 2, and 5 Gy ionizing radiation (12 samples per patient), in a total of 5 individual patients.